Synthesis of a Chiral C2-Symmetric Sterically Hindered Pyrrolidine Nitroxide Radical via Combined Iterative Nucleophilic Additions and Intramolecular 1,3-Dipolar Cycloadditions to Cyclic Nitrones

• Published in: Journal of organic chemistry Vol. 77; no. 23; pp. 10688 - 10698
• Main Authors: Morozov, Denis A., Kirilyuk, Igor A., Komarov, Denis A., Goti, Andrea, Bagryanskaya, Irina Yu, Kuratieva, Natalia V., Grigor'ev, Igor A.
• Format: Journal Article
• Language: English
• Published: WASHINGTON Amer Chemical Soc 07.12.2012; American Chemical Society
• Subjects: Chemistry; Chemistry, Organic; cycloaddition reactions; Lewis bases; moieties; organic chemistry; oxidation; Physical Sciences; Science & Technology; stereoselectivity; STABLE FREE-RADICALS; REGIOSELECTIVE OXIDATION; ISOXAZOLIDINES; X=Y-ZH SYSTEMS; DIASTEREOSELECTIVE SYNTHESIS; REDUCTION; POTENTIAL 1,3-DIPOLES; STEREOSELECTIVE-SYNTHESIS; N-OXIDES; EN-ROUTE
• ISSN: 0022-3263; 1520-6904; 1520-6904
• DOI: 10.1021/jo3019158

A sterically hindered bis-spirocyclic C-2-symmetric chiral pyrrolidine-type nitroxide has been successfully synthesized starting from an L-tartaric derived nitrone. Starting from a pyrrolidine flanked by two methylene groups, complete quaternization of the two alpha-carbon atoms has been accomplished through iteration of completely regio- and stereoselective intramolecular cycloaddition reactions and organometallic additions to key nitrone intermediates, formed in turn by oxidation procedures. This method appears to be very useful for building up bulky spirocyclic moieties adjacent to a nitroxide group and provides an important supplementation to traditional methods of nitroxide synthesis. The synthesized chiral nitroxide showed a very high stability to reduction with ascorbate (k approximate to 8 x 10(-3) M-1 s(-1)).